TY - THES

T1 - Testing Sulforaphane for chemoprevention against ageing and functional decline in male Drosophila models

AU - Bellew-Dunn, Esme

PY - 2020

Y1 - 2020

N2 - Sulforaphane (SFN) has been a phytochemical of interest in targeting severaldiseases. Many of these diseases are age related. Further, we can find evidence in the literature that SFN affects nearly every understood hallmark of ageing. Despite this, very little work has been carried out with SFN in the context of ageing, lifespan and functional health with age. Previous unpublished work has supported the possibility that SFN acts as a hormetic drug to improve lifespan at sub-toxic doses. In this study, SFN was tested in the Drosophila melanogaster model organism, and its effects in lifespan, performance and biochemical hallmarks of ageing were monitored. These were assessed through three full lifespan/survival studies, a negative geotaxis assay, and a quantitative Real-Time Polymerase Chain Reaction experiment to investigate the impact of the drug on antioxidant gene expression. A High-Performance Liquid Chromatography experiment was also carried out to investigate our early findings, and test SFN absorption into fly food. A significant improvement in lifespan was associated with SFN in only very limited conditions. White Dahomey flies reared on sugar-yeast food given 100µg/ml SFN between days 9 and 45 of their lives showed an improvement of 5.74%. Notably, Lancaster flies under identical conditions showed a significant decline (6.34%). No other significant findings were made. These findings may indicate SFN has limited potential as an anti-ageing intervention and its effect is dramatically altered by food conditions, genetic background, and timing of dosage. However, we cannot rule out that these findings were caused by chance, and so recommend further work to verify our findings. We also hypothesise that another compound found in broccoli extract, glucoraphanin, may represent a better target for these studies, as previous work has shown low-SFN content broccoli extract to have a stronger effect than pure SFN.

AB - Sulforaphane (SFN) has been a phytochemical of interest in targeting severaldiseases. Many of these diseases are age related. Further, we can find evidence in the literature that SFN affects nearly every understood hallmark of ageing. Despite this, very little work has been carried out with SFN in the context of ageing, lifespan and functional health with age. Previous unpublished work has supported the possibility that SFN acts as a hormetic drug to improve lifespan at sub-toxic doses. In this study, SFN was tested in the Drosophila melanogaster model organism, and its effects in lifespan, performance and biochemical hallmarks of ageing were monitored. These were assessed through three full lifespan/survival studies, a negative geotaxis assay, and a quantitative Real-Time Polymerase Chain Reaction experiment to investigate the impact of the drug on antioxidant gene expression. A High-Performance Liquid Chromatography experiment was also carried out to investigate our early findings, and test SFN absorption into fly food. A significant improvement in lifespan was associated with SFN in only very limited conditions. White Dahomey flies reared on sugar-yeast food given 100µg/ml SFN between days 9 and 45 of their lives showed an improvement of 5.74%. Notably, Lancaster flies under identical conditions showed a significant decline (6.34%). No other significant findings were made. These findings may indicate SFN has limited potential as an anti-ageing intervention and its effect is dramatically altered by food conditions, genetic background, and timing of dosage. However, we cannot rule out that these findings were caused by chance, and so recommend further work to verify our findings. We also hypothesise that another compound found in broccoli extract, glucoraphanin, may represent a better target for these studies, as previous work has shown low-SFN content broccoli extract to have a stronger effect than pure SFN.

KW - Sulforaphane

KW - Ageing

KW - Drosophila melanogaster

KW - DROSOPHILA

U2 - 10.17635/lancaster/thesis/930

DO - 10.17635/lancaster/thesis/930

M3 - Master's Thesis

PB - Lancaster University

ER -